This project is designed to further develop and strengthen collaborative research on perinatal and neonatal factors associated with neurological impairments in children. The project will be conducted at Sir Ganga Ram Hospital, Delhi, India, working in conjunction with the University of Rochester Medical Center, Rochester, NY. This collaboration was initiated in 2010 with support from an NIH-ICMR funded R03 grant to study jaundice- associated auditory toxicity in infants. The collaboration was strengthened further by our pilot study in term infants, which demonstrated that perinatal latent iron deficiency (P-LID) is associated with abnormal auditory neural myelination (ANM). We now propose a more extensive R01 grant proposal leveraging our joint resources and prior successful collaborations to further develop the capabilities of our Indian collaborators. We will conduct a double-blind randomized clinical trial (DBRCT) and evaluate the efficacy and safety of iron supplementation to improve ANM in term infants with P-LID. Abnormal ANM during the neonatal period has been associated with negative neurodevelopmental outcomes during early childhood. Worldwide, iron deficiency (ID) is the most common preventable nutritional disorder that contributes to abnormal neurological outcome across the life span. Iron is essential for brain myelination which peaks during the perinatal period (2 months before and after birth at term gestation). Currently, the American Academy of Pediatrics recommends that term infants not receive any iron supplementation during the first 4 months of life. However, P-LID (serum ferritin < 76 ng/mL) is common at birth among term infants born to mothers with hypertension, diabetes, or ID anemia during pregnancy. In India, maternal ID during pregnancy and P-LID among term infants are extremely common. P-LID during the critical period of peak brain myelination in neonates has been associated with acute and long-lasting abnormal brain development. These neurodevelopmental disabilities result not only in poor life expectations, but billions of dollars in annual costs globally to provide affected children with care and special education. Therefore, early identification of P-LID and optimal iron supplementation during the critical postnatal period of brain maturation may help to improve brain myelination and prevent neurodevelopmental disabilities. The primary objective of this DBRCT is to determine if oral iron supplementation of 2 or 4 mg/kg/day for 2 months, compared to placebo, will be safe and improve ANM, as evaluated by auditory brainstem evoked response, in 255 term infants with P-LID (165 in India & 90 in the US). In carrying out this DBRCT, we will develop a Center of Excellence in Clinical Research in New Delhi, India, through education, mentoring and high quality research experiences. In the long- term, we aim to determine if improving myelination with iron supplementation will enhance long-term neurodevelopmental outcomes in term infants. Building sustainable research capacity in India to support future collaborative DBRCT that address nervous system impairment during early infancy and childhood will ultimately lead to development of treatment and prevention policies that can be implemented globally.